First Author | Singh R | Year | 2010 |
Journal | Science | Volume | 328 |
Issue | 5984 | Pages | 1394-8 |
PubMed ID | 20538950 | Mgi Jnum | J:172941 |
Mgi Id | MGI:5009354 | Doi | 10.1126/science.1189176 |
Citation | Singh R, et al. (2010) Defective cross-presentation of viral antigens in GILT-free mice. Science 328(5984):1394-8 |
abstractText | Gamma-interferon-inducible lysosomal thiolreductase (GILT) promotes major histocompatibility complex (MHC) class II-restricted presentation of exogenous antigens containing disulfide bonds. Here, we show that GILT also facilitates MHC class I-restricted recognition of such antigens by CD8+ T cells, or cross-presentation. GILT is essential for cross-presentation of a CD8+ T cell epitope of glycoprotein B (gB) from herpes simplex virus 1 (HSV-1) but not for its presentation by infected cells. Initiation of the gB-specific CD8+ T cell response during HSV-1 infection, or cross-priming, is highly GILT-dependent, as is initiation of the response to the envelope glycoproteins of influenza A virus. Efficient cross-presentation of disulfide-rich antigens requires a complex pathway involving GILT-mediated reduction, unfolding, and partial proteolysis, followed by translocation into the cytosol for proteasomal processing. |